Antenatal Infections and their Consequences

Certain maternal infections can have serious long-term consequences for the fetus.

Rubella is a viral infection causing a pink rash, with swelling of lymph glands behind the ears and at the back of the head. There are mild constitutional symptoms and occasionally joint pain in adults.¹

Management

With rubella-like rash, test for rubella and parvovirus B19 (even if reported to be immune); test serum for IgG and IgM and repeat if results equivocal. Rising levels suggest recent infection (consult virologist).

Evidence of infection should be discussed with the patient with a view to considering termination.²

Prevention is by measles, mumps and rubella (MMR) vaccine in second year of life plus pre-school booster with antenatal screening for rubella susceptibility.

Consequences

If rubella is contracted within first 11 weeks of pregnancy there is a 90% chance of the fetus being affected.¹ This falls to 20% during weeks 11-16. In weeks 16-20 there is a slight risk of deafness and, after that, no increased risk.
Fetal defects associated with fetal rubella syndrome include:

• Mental handicap
• Cataracts
• Deafness
• Heart defects
• Intrauterine growth retardation
• Inflammation of brain, liver, lungs and bone marrow

This is characterised by fever, malaise and a pruritic rash that develops into crops of maculopapules, which become vesicular and crust over before healing. The incubation period is 10-21 days and the disease is infectious 48 hours before the rash appears and continues to be infectious until the vesicles crust over.³

More than 90% of the antenatal population are seropositive for varicella immunoglobulin G (IgG) antibody, so although contact with chickenpox is common in pregnancy, primary infection is uncommon. It is estimated to complicate three in every 1,000 pregnancies.⁴

Management

• Establish whether mother is immune.³
• If any doubt, request antibody levels.
• Liaise with local microbiology for advice.
• Varicella-zoster immunoglobulin (VZIG) may be indicated.

Consequences

In adults, chickenpox is associated with greater morbidity - pneumonia (10% pregnant women), hepatitis and encephalitis.
It may also cause fetal varicella syndrome (FVS), previously known as congenital varicella syndrome or varicella infection of the newborn.

Before 20 weeks of gestation:

• Chickenpox in the first trimester does not increase the risk of spontaneous miscarriage.⁴
• FVS is characterised by one or more of the following:
  • Skin scarring in a dermatomal distribution.
  • Microphthalmia, chorioretinitis and cataracts.
  • Hypoplasia of the limbs.
  • Neurological abnormalities, e.g. microcephaly, cortical atrophy, mental retardation and dysfunction of bowel and bladder sphincters.

• This does not appear to be associated with adverse effects in the fetus.
• It may present as shingles in the first few years of infant life.

• Up to 50% of babies are infected, and approximately 23% of these develop clinical varicella despite high titres of passively acquired maternal antibody.
• The most severe chickenpox occurs if the infant is born within 7 days of onset of the mother's rash.

In adolescence and early adulthood cytomegalovirus (CMV) causes a febrile illness with splenomegaly, impaired liver function and abnormal lymphocytes in the blood.²

Consequences

• 1-2% of seronegative pregnant women have a primary infection during their pregnancy; a small proportion undergo reactivation.
• Effect on fetus is more severe from a primary infection
• Approximately 1% die at, or soon after, birth
• 4% have severe cytomegalic disease; most frequent signs are:
  • Low birth weight
  • Hepatosplenomegaly
  • Jaundice
  • Thrombocytopenia
  • Petechiae and/or purpura
  • Microcephaly
  • Intracranial calcifications
  • Choroidoretinitis
  • Deafness
  • Speech defects
  • Mental retardation, which may appear later
• 15% appear normal, but hearing defects and possible mental retardation become apparent later in life.

Infection with the parasite Toxoplasma gondii, a coccidian, with the cat as its definitive host.

Acute acquired toxoplasmosis presents with fatigue lasting for several weeks, headache, muscle pain, low-grade fever for one or several weeks. Usually sub-clinical with lymphadenopathy affecting the posterior cervical, suboccipital, retroauricular or submental nodes. These can be painful and tender for 1-2 weeks and rarely larger than walnuts, being small, well defined and mobile.⁵

Management

Treat with spiramycin throughout pregnancy, with regular ultrasound examination of fetus.

Consequences

A third of infants become infected if mother becomes infected during pregnancy, especially in later pregnancy. There are many different forms of presentation.

• Systemic disease of neonate:
  • Rash
  • Jaundice
  • Thrombocytopenic purpura
  • Hepatosplenomegaly
  • Pneumonia
  • Progressive uveitis
• Neurological disease:
  • Hydrocephalus; due to stenosis of the duct of Sylvius requiring shunt
  • Microcephaly
  • Microphthalmia
  • Retinochoroiditis
  • Cerebral calcification
• Mild disease; small area of retinochoroiditis or slight cerebral calcification without signs of brain damage.
• Sub-clinical; occurs in 70% of infected babies.
• Relapsing; retinochoroiditis as flare-ups can occur at any age, most cases in a previously intact retina.

Pelvic inflammatory disease (PID) includes infections of the upper genital tract and is commonly caused by sexually transmitted infections. Chlamydia has been identified in 52% of cases of confirmed PID and gonorrhoea in 14%.
Presents with lower abdominal pain and tenderness. Also possibly dyspareunia, abnormal vaginal bleeding and/or discharge. Many cases are asymptomatic.

Management

Pregnant women with PID should be admitted for IV antibiotics:^6,7

• Ceftriaxone has not specifically been studied during pregnancy. However, the risk associated with use of cephalosporins during pregnancy is thought to be low and, although data are limited for individual agents such as ceftriaxone, the cephalosporins as a class are considered to be an appropriate choice during pregnancy.
• Doxycycline is contra-indicated beyond the 15th week of gestation because, from the 16th week of pregnancy, it causes tooth and bone discolouration and inhibits bone growth. However, it can be used in the first trimester. Inadvertent first-trimester use of tetracyclines occurs frequently and has not been associated with an increased risk of congenital malformations.
• Metronidazole has been in clinical use for a long time, and experience suggests that it is not teratogenic in humans.
• Ofloxacin has only limited pregnancy-exposure data. However, a recent study did not find that quinolone use in the first trimester of pregnancy was associated with an increased risk of malformations or other adverse effects on pregnancy outcome.
• There are fewer published data on the use of azithromycin rather than erythromycin during pregnancy and breastfeeding. The limited published data do not demonstrate an increased risk of congenital malformations following exposure to azithromycin in human pregnancy.

Consequences

• PID is associated with increase in preterm delivery, maternal and fetal morbidity.
• Can also transmit ophthalmia neonatorum which is potentially sight threatening.

Genital herpes simplex produces patches of small, fluid-filled vesicles that burst to form shallow, painful ulcers. Initial infection is followed by recurrences and both occur as self-limiting episodes.⁸

Management

• Main risk of transmission is during primary infection when oral aciclovir should be considered in the first 6 months of pregnancy.⁹
• After that, and in cases of recurrence with active genital lesions, may need to offer Caesarean section.

Consequences

Neonatal infection is rare in the UK but can have serious effect upon the fetus if it disseminates, e.g. encephalitis.

Human immunodeficiency virus (HIV) affects T-lymphocytes, macrophages and monocytes with the CD4 receptor. It attacks the immune system, usually over many years, and reduces its effectiveness until an AIDS-defining illness occurs. HIV transmission to the baby is a significant problem, especially in the developing world.
Maternal transmission can occur via the following routes:¹⁰

• In utero by passage of virus across the placenta
• During delivery, from blood and placental fluids
• From breast milk

Management

Transmission can be reduced by:¹¹

• Maternal treatment with antiretrovirals
• Caesarean section
• Avoidance of breast-feeding

Consequences

Untreated, most maternally infected children die by age 10 years.

Asymptomatic bacteriuria is very common in pregnant women because of the altered dynamics of the urinary tract. If untreated, this frequently progresses to urinary tract infection (UTI) - either acute cystitis (1-2%) and/or pyelonephritis.¹² The symptoms of acute cystitis are the same as in non-pregnant women:

• Frequency
• Urgency
• Cloudy, smelly urine
• Dysuria and strangury

Those of acute pyelonephritis are:

• Pyrexia
• Rigors
• Flank pain
• Nausea & vomiting
• Headache
• Frequency & dysuria

Management

Urine should be tested by dipstick at the first antenatal visit. Confirmation is with urine microscopy and culture.
Treat with trimethoprim, a cephalosporin or nitrofurantoin (except where otherwise contra-indicated). In recurrent UTI, consider prophylactic nitrofurantoin but stop before delivery.

Consequences

UTI increases the risk of premature labour and low birth weight.

1. HPA - Rubella (German Measles) - General Information. Health Protection Agency.
2. Tookey PA & Logan S in Oxford Textbook of Medicine, 4th Edition. Eds; Warrell DA et al. OUP 2003.
3. Chickenpox, Clinical Knowledge Summaries (January 2008)
4. Chickenpox in pregnancy, Royal College of Obstetricians and Gynaecologists (September 2007)
5. Couvreur J and Thulliez Ph in Oxford Textbook of Medicine, 4th Edition. Eds; Warrell DA et al. OUP 2003.
6. Pelvic inflammatory disease, Clinical Knowledge Summaries (August 2009)
7. Management of acute pelvic inflammatory disease, Royal College of Obstetricians and Gynaecologists (2008)
8. Herpes simplex - genital, Clinical Knowledge Summaries (September 2008)
9. Management of genital herpes, British Association for Sexual Health & HIV (2007)
10. Frye R, Rivera-Hernandez D; HIV Infection. eMedicine, June 2007; Overview of congenital and paediatric HIV infection.
11. Management of HIV in pregnancy, Royal College of Obstretricians and Gynaecologists (2004)
12. Urinary tract infection (lower) - women, Clinical Knowledge Summaries (October 2009)

• Antenatal care: routine care for the healthy pregnant woman, NICE Clinical Guideline (March 2008)
• Guidelines on the management of and exposure to rash illness in pregnancy, Health Protection Agency (2003); (including consideration of relevant antibody screening programmes in pregnancy)